代谢组学在脊柱结核血清诊断标志物筛选中的应用

Application of metabolomics in screening serum diagnostic biomarkers for spinal tuberculosis

目的:分析脊柱结核(STB)患者血清代谢特征,筛选潜在诊断生物标志物。方法:收集2020年1月至2022年1月于宁夏医科大学总医院骨科确诊的25例STB患者作为实验组,25例健康体检者作为对照组。应用超高效液相色谱串联四极杆飞行时间质谱技术检测两组血清中的代谢物,结合两独立样本t检验等单变量统计分析方法和主成分分析、偏最小二乘判别分析等多元统计分析筛选STB患者血清中主要的差异代谢物,并进行受试者工作特征曲线分析评估其诊断效能。结果:共检测到4755种代谢物,实验组血清中差异表达的代谢物共有570种,其中343种上调,227种下调。生物信息分析结果显示,差异代谢物主要富集在不饱和脂肪酸的生物合成、卟啉代谢、组氨酸代谢、β-丙氨酸代谢、泛酸和辅酶A的生物合成等通路。磷脂酰胆碱(O-13:0/O-1:0)、溶血磷脂酰乙醇胺[(18∶1(11Z)/0∶0)]、Palmitoleoyl-ethanolamine在实验组的含量均低于对照组(493.170比123.463,t=-6.390,P<0.01;239.196比14.708,t=-11.019,P<0.01;83.096比12.273,t=-4.030,P<0.01),差异有统计学意义;在诊断STB时,曲线下面积分别为0.997、0.995、0.981。结论:实验组和对照组代谢差异有统计学意义,磷脂酰胆碱(O-13:0/O-1:0)、溶血磷脂酰乙醇胺[(18∶1(11Z)/0∶0)]、Palmitoleoyl-ethanolamine对STB具有良好的诊断效能。

Objective Analyze the serum metabolic profiles of spinal tuberculosis(STB)patients and screen potential diagnostic biomarkers.Methods 25 STB patients diagnosed in the Department of Orthopedics,General Hospital of Ningxia Medical University from January 2020 to January 2022 were collected as the experimental group,25 healthy physical examiners were collected as the healthy control group.Using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry technology to detect metabolites in the serum of the two groups,combining univariate statistical analysis methods such as two independent samples t-test and multivariate statistical analysis such as principal component analysis and orthogonal projections to latent structures-discriminant analysis to screen for the major differential metabolites in the serum of STB patients,and conduct receiver operating characteristic curve analysis to evaluate their diagnostic efficacy.Results A total of 4755 metabolites were detected.570 metabolites were differentially expressed in the serum of experimental group,of which 343 were upregulated and 227 were downregulated.Bioinformatics analysis revealed that differential metabolites were mainly enriched in the Biosynthesis of unsaturated fatty acids,Porphyrin metabolism,Histidine metabolism,beta-Alanine metabolism,Pantothenate and CoA biosynthesis pathways.The contents of PC(O-13:0/O-1:0),LysoPE[(18∶1(11Z)/0∶0)],and Palmitoleoyl-ethanolamine in the experimental group were lower than those in the control group(493.170 vs.123.463,t=-6.390,P<0.01;239.196 vs.14.708,t=-11.019,P<0.01;83.096 vs.12.273,t=-4.030,P<0.01),with statistically significant differences;when diagnosing STB,the areas under the curve were 0.997,0.995,and 0.981,respectively.Conclusion There were significant differences in metabolism between the experimental and control groups,PC(O-13:0/O-1:0),LysoPE[(18∶1(11Z)/0∶0)],and Palmitoleoyl-ethanolamine had good diagnostic efficacy for STB.